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CHAPTER 4 4.1 Abstract Many spinal cord injured patients develop neuropathic pain, which may be driven by spinal cord inflammatory mediators. It was previously demonstrated that treatment using 670 nm (red) light irradiation alters microglia/macrophage responses and alleviates mechanical hypersensitivity at 7 days post-injury. Here, the effects of red light on the development of mechanical hypersensitivity following spinal cord injury preceding the 7 days post-injury, and on pain associated cells and cytokines were investigated. A mild T10 hemicontusion spinal cord injury was induced in 8- week-old male Wistar rats (n = 64). Two additional age-matched groups received sham surgeries (n = 18). A subset of animals was subjected to daily red light-treatment (30 min/day; 670 nm LED; 35 mW/cm2). Mechanical sensitivity of the rat dorsum was assessed from 1 day post-injury and repeated every second day. The spinal cords of these animals were also collected from 1, 3, 5 and 7 days post-injury for analysis of astrocyte activation (GFAP) and pro-inflammatory markers (IL1β and iNOS) in microglia/macrophages at the injury level. Red light treatment significantly reduced the chance of developing mechanical hypersensitivity following spinal cord injury (p < 0.05) for the first 5 days. This effect was accompanied by a reduction in astrocyte activation (p < 0.05) and a reduction in iNOS expression in IBA1+ cells (p < 0.05). However, IL1β expression in GFAP+ and IBA1+ cells were not altered by red light treatment throughout the recovery period. The results indicate that red light treatment decreases the development of mechanical hypersensitivity over the first 5 days post-injury while reducing mechanical sensitivity in normosensitive animals. These effects are associated with reduced iNOS expression in microglia/macrophages and a reduction in astrocytes that do not express IL1β. 4.2 Introduction The World Health Organisation estimates between 250,000 and 500,000 people suffer from spinal cord injury each year globally with an incidence of up to 1000 per million (Singh et al., 2014; World Health Organization and International Spinal Cord Society, 2013). About 65-80% of spinal cord injured patients develop neuropathic pain (NP) (Dijkers et al., 2009; Jensen and Finnerup, 2014; Pascoal-Faria et al., 2015; Turner et al., 2001) which is considered severe in 20-30% of cases (Bryce, 2009). Multi-therapeutic approaches utilising combinations of pharmacological intervention, exercise, massage and physiotherapy are often employed to manage NP, however, these approaches require significant resources from different professionals and family members, and are generally inefficient (Bryce, 2009; Widerstrom-Noga et al., 2014). Hyperalgesia and allodynia are two NP characteristics where the pain threshold is reduced, resulting in an “exaggeration” or “false alarm” of pain perception respectively (Jensen and Finnerup, 2014). The understanding of the mechanisms of NP development remain incomplete, but there is consensus that NP following spinal cord injury is implicated with alterations in the central nervous systems (D'Angelo et al., 2013). Activated glial cells, namely microglia/macrophages and astrocytes, have long been associated with both the development and 80PDF Image | Effects of Red Light Treatment on Spinal Cord Injury
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